Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of CD4+ T-helper (Th) cell responses is likely to be an important requirement of vaccine candidates designed to prevent or moderate human immunodeficiency virus-1 (HIV-1) infection. We have investigated the ability of hybrid Ty virus-like particles carrying the V3 loop region of the HIV-1 IIIB envelope gp120 (V3:Ty-VLP) to elicit V3-specific proliferative responses. Significant proliferation in response to stimulation in vitro with homologous IIIB V3 peptide was observed following immunization of mice with V3:Ty-VLP either as an aluminium hydroxide precipitate or without adjuvant. Responses to MN V3 peptide were also observed in certain mouse haplotypes. To assess the effect of presenting the V3 loop in this particulate form, we compared the responses induced by V3:Ty-VLP with those obtained with two non-particulate immunogens, recombinant gp120 (rgp120) and V3 peptide conjugated to albumin. V3-specific responses to V3 peptide in vitro were reproducibly higher following immunization with V3:Ty-VLP than with either rgp120 or V3-albumin coagulate (V3-alb). The data indicate that immunization with the V3 loop as a hybrid Ty-VLP results in enhanced proliferative responses to V3 peptide and recognition of rgp120 in vitro. Some cross-reactivity of Th cells for V3 sequences from different isolates was also observed.
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PMID:Enhanced proliferative cellular responses to HIV-1 V3 peptide and gp120 following immunization with V3:Ty virus-like particles. 136 83

The yeast retrotransposon, Ty, encodes a set of proteins that are assembled into virus-like particles, Ty-VLPs (refs 1, 2). These proteins include Ty-VLP structural proteins, a protease that mediates cleavage of primary translation products and a reverse transcriptase. The major structural components of Ty-VLPs are proteolytic products of the primary translation product, p1 (ref. 3). We have recently shown that protein p1 alone can form Ty-VLPs (ref. 3). Here we demonstrate that p1 fusion proteins, comprising most of p1 and part of human immunodeficiency virus (HIV) protein gp120, form hybrid HIV:Ty-VLPs. These hybrid particles provide a rapid means of preparing and evaluating HIV antigens for a variety of immunological purposes.
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PMID:The expression of hybrid HIV:Ty virus-like particles in yeast. 304 Dec 26

In studies of the natural history of human immunodeficiency virus type 1 (HIV-1) infection, it has been repeatedly shown that higher-titer antibody responses to the HIV gag p24 protein correlate with less rapid disease progression. In HIV-negative persons, immunization with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) induced humoral and cellular immune responses to p24. This construct was therefore studied as a potential immunotherapeutic agent with the objective of augmenting the immune response to p24 in a double-blind placebo-controlled trial involving 74 p24 antibody-positive, asymptomatic HIV-1-infected subjects with CD4 cell counts > 350/mm3. Immunization with p24-VLP was generally well tolerated. Immunization with p24-VLP did not increase p24 antibody levels and had no effect on CD4 cell counts or virus load. The failure to increase p24 antibody titers cannot entirely be explained by the subjects' immunodeficiency because most generated an antibody response to Ty, a yeast component of the immunogen.
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PMID:Immunization with recombinant p17/p24:Ty virus-like particles in human immunodeficiency virus-infected persons. 884 31

Noninfectious Pr55gag virus-like particles containing high quantities of oligomeric human immunodeficiency virus type 1 (HIV-1) envelope (Env) proteins represent potential candidate immunogens for a vaccine against HIV-1 infection. Thus, chimeric env genes were constructed encoding the HIV-1 exterior glycoprotein gp120 which was covalently linked at different C-terminal positions to a transmembrane domain (TM) from the Epstein-Barr virus (EBV) major Env glycoprotein gp220/ 350. All chimeric Env-TM polypeptides as well as the wild-type HIV Env proteins were equally produced and incorporated at the outer surface of insect cells using the baculovirus expression system. In the presence of coexpressed HIV Pr55gag polyproteins significantly decreased amounts of wild-type Env proteins were presented at the cell surface, whereas the membrane incorporation of the Env-TM chimeras was not affected. Biochemical and immunoelectron microscopical analysis of particles that were efficiently released from these cells displayed the incorporation of both wild-type Env and chimeric Env-TM proteins on the surface of VLPs. However, the quantities of particle-associated chimeric Env-TM proteins exceeded those of incorporated wild-type Env proteins by a factor of 5-10. Chemical cross-linking and subsequent polyacrylamide gel electrophoresis of VLP-entrapped Env proteins revealed that the chimeric Env-TM proteins form homodimers and a higher-order oligomer, similar to that observed for wild-type Env proteins. Thus, the results of this study clearly demonstrate that the replacement of the gp41 transmembrane protein of gp160 by a heterologous, EBV gp220/350-derived membrane anchor provides an effective strategy to incorporate high quantities of oligomeric HIV gp120 proteins on the surface of Pr55gag virus-like particles.
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PMID:Increased incorporation of chimeric human immunodeficiency virus type 1 gp120 proteins into Pr55gag virus-like particles by an Epstein-Barr virus gp220/350-derived transmembrane domain. 930 33

The human immunodeficiency virus type 1 (HIV-1) Gag precursor Pr55(gag) by itself is capable of assembling into retrovirus-like particles (VLP). In the present study, we attempted to identify the minimal Gag sequences required for the formation of VLP. Our results show that about 80% of Pr55(gag) can be either deleted or replaced by heterologous sequences without significantly compromising VLP production. The smallest chimeric molecule still able to efficiently form VLP was only about 16 kDa. This minimal Gag construct contained the leucine zipper domain of the yeast transcription factor GCN4 to substitute for the assembly function of nucleocapsid (NC), followed by a P-P-P-P-Y motif to provide late budding (L) domain function, and retained only the myristylation signal and the C-terminal capsid-p2 domain of Pr55(gag). We also show that the L domain function of HIV-1 p6(gag) is not dependent on the presence of an active viral protease and that the NC domain of Pr55(gag) is dispensable for the incorporation of Vpr into VLP.
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PMID:Efficient particle production by minimal Gag constructs which retain the carboxy-terminal domain of human immunodeficiency virus type 1 capsid-p2 and a late assembly domain. 1082 43

Human immunodeficiency virus (HIV) type 1-infected (HIV-positive) and -uninfected (HIV-negative) sex workers were examined for the presence of cervical human papillomavirus (HPV) DNA. Cervicovaginal rinse and serum samples from these women were examined for IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) by ELISA. The HIV-positive women displayed a significantly higher prevalence of HPV DNA (40/47 [85%]) than did the HIV-negative women (22/52 [42%]; P=.00001). Both HIV-positive and HIV-negative sex workers displayed a high seroprevalence rate for anti-VLP-16 IgG antibodies (27/40 [68%] and 30/43 [70%], respectively), but significantly fewer HIV-positive women than HIV-negative women had anti-VLP-16 serum IgA (6/40 [15%] vs. 17/43 [40%], respectively; P=.012). Significantly more HIV-positive women than HIV-negative women had cervical anti-VLP-16 IgG antibodies (16/49 [33%] vs. 6/63 [10%], respectively; P=.002) but not IgA antibodies (P=.3).
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PMID:The impact of human immunodeficiency virus type 1 status on human papillomavirus (HPV) prevalence and HPV antibodies in serum and cervical secretions. 1097 25

Papillomavirus-like particle (VLP)-based subunit vaccines have undergone rapid development over the past 8 years. Three types are being investigated. The most basic type is composed of only the L1 major capsid protein and is designed to prevent genital human papillomavirus (HPV) infection by inducing virus-neutralizing antibodies. On the basis of positive results in animal models, clinical trials of this type of vaccine for HPV16, and other types, are currently under way. Preliminary results have been encouraging in that systemic immunization with the L1 VLPs induced high serum titers of neutralizing antibodies without substantial adverse effects. The second type of vaccine incorporates other papillomavirus polypeptides into the VLPs as L1 or L2 fusion proteins. These chimeric VLPs are designed to increase the therapeutic potential of an HPV vaccine by inducing cell-mediated responses to nonstructural viral proteins, such as E7. Studies in mice indicate that these vaccines generate potent antitumor cytotoxic lymphocyte (CTL) responses while retaining the ability to induce high-titer neutralizing antibodies. It is likely that prophylactic and therapeutic clinical trials of chimeric VLPs will be initiated in the near future. The third type of VLP-based vaccine is designed to induce autoantibodies against central self-antigens by incorporating self-peptides into the outer surface of VLPs, a process that could have therapeutic potential in various disease settings unrelated to HPV infection. In a recent proof of concept study, a peptide from an external loop of mouse CCR5 protein was inserted into a neutralizing epitope of L1. In mice, the particles generated by this chimeric L1 were able to induce high titers of CCR5 antibodies that specifically recognized the surface of CCR5-transfected cells and blocked in vitro infection of an M-tropic human immunodeficiency virus strain.
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PMID:Papillomavirus-like particle vaccines. 1115 7

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML). As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.
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PMID:Cellular and humoral immune response in progressive multifocal leukoencephalopathy. 1135 54

Long-term effects of therapeutic vaccination of human immunodeficiency virus (HIV)-1-infected subjects with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) on progression to AIDS, death, a CD4 cell count <or=200 cells/mm(3) and CD4 cell count decline were studied in a multicenter cohort study of 56 individuals who participated in a phase II double-blind placebo-controlled trial with p24-VLP in 1993. Using Cox proportional hazard analysis, no difference between vaccine and placebo groups was found in progression to death (adjusted hazard rate (HR): 0.68 (95% CI: 0.05-7.83), AIDS (adjusted HR: 1.07 (95% CI: 0.21-5.36)) and a CD4 cell count <or=200 cells/mm(3) (adjusted HR: 1.00 (95% CI: 0.35-2.87)). Using linear regression with correction for multiple visits within one person, no effect of vaccination on CD4 cell count decline, adjusted for antiretroviral therapy (ART) use, was found (P=0.98). In conclusion, therapeutic vaccination with p24-VLP is not related to slower HIV-1 disease progression.
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PMID:Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression. 1200 90

By using a baculovirus expression system, we have successfully produced simian immunodeficiency virus (SIV)-like particles (VLPs) with high levels of biologically active SIV envelope (Env) incorporated on their surfaces. To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route. High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent. The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented. Mice immunized with VLPs plus CT were found to exhibit higher serum antibody responses than those immunized with VLPs alone (P<0.001). Furthermore, IgA antibody production was detected in both saliva and vaginal fluid from mice mucosally immunized with SIV VLPs. Higher levels of IgA were found in vaginal fluid than in saliva in animals immunized with SIV VLPs plus CT (P<0.05). Higher neutralizing activity to SIV 1A11 was also found in serum of animals immunized with SIV VLPs plus CT. Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT. These results suggest that VLPs are effective mucosal antigens that can induce both humoral and cellular immune responses at systemic and mucosal sites.
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PMID:Intranasal immunization with SIV virus-like particles (VLPs) elicits systemic and mucosal immunity. 1205 10


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